title: Pharmacophore modeling and docking studies on some nonpeptide-based caspase-3 inhibitors.
abstract: Neurodegenerative disorders are major consequences of excessive apoptosis caused by a proteolytic enzyme known as caspase-3. Therefore, caspase-3 inhibition has become a validated therapeutic approach for neurodegenerative disorders. We performed pharmacophore modeling on some synthetic derivatives of caspase-3 inhibitors (pyrrolo[3,4-c]quinoline-1,3-diones) using PHASE 3.0. This resulted in the common pharmacophore hypothesis AAHRR.6 which might be responsible for the biological activity: two aromatic rings (R) mainly in the quinoline nucleus, one hydrophobic (H) group (CH₃), and two acceptor (A) groups (-C=O). After identifying a valid hypothesis, we also developed an atom-based 3D-QSAR model applying the PLS algorithm. The developed model was statistically robust (q² = 0.53; pred_r² = 0.80). Additionally, we have performed molecular docking studies, cross-validated our results, and gained a deeper insight into its molecular recognition process. Our developed model may serve as a query tool for future virtual screening and drug designing for this particular target.
authors.affiliation: Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar, Madhya Pradesh 470003, India.
authors.forename: Simant
authors.initials: S
authors.lastname: Sharma
authors.forename: Arijit
authors.initials: A
authors.lastname: Basu
authors.forename: R K
authors.initials: RK
authors.lastname: Agrawal
mesh_terms: D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship; D011804:Quinolines / Q000737:chemistry
chemical_list: D061945:Caspase Inhibitors; D011804:Quinolines; C037219:quinoline; D053148:Caspase 3